Development of materials that do not induce hostile response from the body tissues upon implantation or insertion in a human or animal body is an important target in the medical device field. In practice, many commonly used materials including plastics, ceramics, and metals have substantial biocompatibility problems.
One important property for medical devices that contact blood after implantation or insertion in a human or animal body is thrombogenicity. Thrombogenicity is the ability of the device to induce formation of blood clots. For blood to clot, it is believed that thrombin must be generated in the blood. Several potent anticoagulants are known that are able to prevent formation of thrombin. The most widely used anticoagulant used during surgical procedures is heparin. When heparin is immobilized on the surface of a medical device, the ability of the surface to induce formation of clots decreases, or in other words, the surface becomes antithrombogenic. However, the antithrombogenicity of a heparinized surface tends to decrease as the surface heparin loses its potency to retard clot formation. Many heparinized surfaces tend to have poor stability in vivo. New heparin compositions and coatings are needed to improve the antithrombogenic stability of heparinized surfaces.
A few reports of heparin compositions and methods of making and using heparin and antithrombogenic compositions have appeared in the art, some examples of which may be found in the patents and publications listed in Table 1 below.
TABLE 1Patents and PublicationsPatent/Publication No.Inventor(s)Issue/Publication DateU.S. Pat. No. 6,143,354Koulik et al. 7 Nov. 2000U.S. Pat. No. 6,110,483Whitbourne et al.29 Aug. 2000U.S. Pat. No. 6,096,726Opolski 1 Aug. 2000U.S. Pat. No. 6,024,918Hendriks et al.15 Feb. 2000U.S. Pat. No. 5,951,586Berg et al.14 Sep. 1999U.S. Pat. No. 5,945,457Plate et al.31 Aug. 1999U.S. Pat. No. 5,879,697Ding et al. 9 Mar. 1999U.S. Pat. No. 5,782,908Cahalan et al.21 Jul. 1998U.S. Pat. No. 5,741,551Guire et al.21 Apr. 1998U.S. Pat. No. 5,616,338Fox, Jr. et al. 1 Apr. 1997U.S. Pat. No. 5,607,475Cahalan et al. 4 Mar. 1997U.S. Pat. No. 5,569,463Helmus et al.29 Oct. 1996U.S. Pat. No. 5,541,167Hsu et al.30 Jul. 1996U.S. Pat. No. 5,455,040Marchant 3 Oct. 1995U.S. Pat. No. 5,447,724Helmus et al. 5 Sep. 1995U.S. Pat. No. 5,441,759Crouther et al.15 Aug. 1995U.S. Pat. No. 5,356,433Rowland et al.18 Oct. 1994U.S. Pat. No. 5,270,046Sakamoto et al.14 Dec. 1993U.S. Pat. No. 5,077,372Hu et al.31 Dec. 1991U.S. Pat. No. 5,061,738Solomon et al.29 Oct. 1991U.S. Pat. No. 5,032,666Hu et al.16 Jul. 1991U.S. Pat. No. 4,786,556Hu et al.22 Nov. 1988U.S. Pat. No. 4,720,512Hu et al.19 Jan. 1988U.S. Pat. No. 4,678,660McGary et al. 7 Jul. 1987U.S. Pat. No. 4,642,242Solomon et al.10 Feb. 1987U.S. Pat. No. 4,613,665Larm23 Sep. 1986U.S. Pat. No. 4,600,652Solomon et al.15 Jul. 1986U.S. Pat. No. 4,529,614Burns16 Jul. 1985U.S. Pat. No. 4,331,697Kudo et al.25 May 1982U.S. Pat. No. 3,846,353Grotta 5 Nov. 1974Technical Publications
Dow Corning MDX4-4159 Fluid 50% Medical Grade Dispersion, Product Information Sheet, Copyright 2000
All patents and publications listed in Table 1 above are hereby incorporated by reference herein in their respective entireties. As those of ordinary skill in the art will appreciate readily upon reading the Summary of the Invention, Detailed Description of the Preferred Embodiments, and claims set forth below, many of the devices and methods disclosed in the patents and publications of Table 1 may be modified advantageously by using the teachings of the present invention.